Idiopathic Ulcers Research Articles

Etiology of esophageal disease in human immunodeficiency virus-infected patients who fail antifungal therapy

To determine the etiologies of esophageal symptoms in human immunodeficiency virus (HIV)-infected patients failing antifungal treatment. Between August 1, 1990 and December 31, 1994, all HIV-infected patients seen at a large inner-city hospital who had esophageal complaints despite being on antifungal therapy were prospectively evaluated for the cause of symptoms. Thus, the population studied included patients given empiric antifungal therapy for esophageal symptoms and patients who developed symptoms while on long-term antifungal therapy. Endoscopy was performed in all patients. The cause of symptoms was determined by the clinical, endoscopic, and pathologic findings, and follow-up after treatment. Over the 53-month study period, 74 patients failing empiric antifungal therapy were identified. The majority (77%) of these patients had esophageal ulcers; 25 patients had idiopathic ulcers and 24 had cytomegalovirus. In 2 patients, Candida was present with other causes of ulcerative esophagitis. Candida esophagitis alone was diagnosed in only 3 patients. No endoscopic abnormalities were observed in 14 patients (19%). An additional 24 patients developed esophageal symptoms while receiving antifungal therapy; endoscopic findings in these patients included ulceration in 16 (67%), Candida esophagitis alone in 2, and normal in 6. Empirically treated patients in whom odynophagia was not the only symptom, those with dysphagia alone, and those with a CD4 count > 100/mm3 were less likely to have an endoscopic diagnosis. Esophageal ulceration is the most common cause of esophageal symptoms in HIV-infected patients failing empiric antifungal therapy and those developing symptoms while receiving antifungal agents. Given these findings, endoscopy should be the test of choice for these nonresponders, rather than escalating the dose of antifungal agent, adding other empiric treatments, or performing barium esophagography.

Thalidomide treatment for idiopathic esophageal ulcers in patients with HIV

Esophageal ulcers may cause troubling symptoms in patients infected with human immunodeficiency virus (HIV). The ulcers are hyperalgic, interfere with nutrition, and cause general debilitation.1 The ulcers can occur as a result of infection from Candida, herpes simplex virus, or more commonly from cytomegalovirus. The ulcers may also form as a result of malignant diseases such as Kaposi\'s sarcoma or lymphoma. When investigation fails to reveal a cause for the ulcers, many patients are treated empirically with oral corticosteroids.

Symptom-specific use of upper gastrointestinal endoscopy in human immunodeficiency virus-infected patients yields high dividends.

The yield of upper gastrointestinal endoscopy (esophago-gastroduodenoscopy; EGD) in human immunodeficiency virus (HIV)-infected patients based on presenting symptoms has not been well studied. We studied consecutive patients with documented HIV infection undergoing EGD at a large innercity hospital between August 1, 1990 and December 31, 1993; all had presenting symptoms and indications for EGD prospectively recorded at the time of EGD. All endoscopic abnormalities were routinely subjected to biopsy, and extensive histopathological evaluation was performed. EGD was considered helpful when the findings stimulated specific therapeutic intervention other than antifungal or antacid medications. The specific indications for EGD in 156 patients were as follows: esophageal symptoms, 102 patients (65%); abdominal pain, 18 (12%); upper gastrointestinal bleeding, 25 (16%); refractory nausea and vomiting, 11 (7%). Overall, pathologic findings were identified in 116 patients (74%): in refractory esophageal symptoms, 82%; upper gastrointestinal bleeding, 92%; abdominal pain, 39%; nausea and vomiting, 27%. EGD with biopsy identified a specifically treatable opportunistic disorder other than Candida in 80 patients (51%), including idiopathic esophageal ulcer (22%) or viral esophagitis and/or duodenitis (29%). EGD was not helpful in 22.3% of cases, those involving Candida (12.3%) and peptic ulcer disease (PUD)-related causes (10%). The mean CD4 count of patients with opportunistic pathologic findings (24/mm3, n = 79) was significantly lower than that of patients with PUD/gastroesophageal reflux disease (GERD) (167/mm3, n = 9) or negative EGDs (165/mm3, n = 35). Overall, the results of EGD influenced patient management in 78% of cases. We conclude that selective symptom-specific use of EGD, particularly in patients with esophageal symptoms refractory to antifungal therapy or gastrointestinal bleeding, usually identifies specifically treatable abnormalities, whereas EGD is less useful for the evaluation of abdominal pain or nausea and vomiting.

Prospective evaluation of biopsy number for the diagnosis of viral esophagitis in patients with HIV infection and esophageal ulcer

Background: Establishing a diagnosis of viral esophagitis in patients with human immunodeficiency virus (HIV) infection has important clinical relevance. However, the number of biopsies required to diagnose viral esophagitis is currently unknown. Methods: Over a 34-month period, all HIV-infected patients with esophageal ulcer underwent 10 biopsies of the largest and/or most accessible lesion, primarily from the ulcer base. The first 3 specimens were placed in one formalin container, the second 3 in another, and 4 additional specimens in the third. Standard histopathologic methods were employed, as well as in situ hybridization or immunohistochemical studies in most patients, and viral cytopathic effect was defined using previously proposed criteria. Patients were then treated on the basis of the results of the initial biopsy specimens with both clinical and endoscopic follow-up. Results: One hundred HIV-infected patients with esophageal ulcer were studied. Cytomegalovirus (CMV) was considered etiologic in 50 patients. Of these 50 patients, the first three biopsy specimens were sufficient to diagnosisCMV in 40 (80%). In 5 patients (10%), the first two sets were negative with only the third set of biopsies positive. Similarly, of the 4 patients with simultaneous CMV and herpes simplex virus (HSV) esophagitis, three sets of biopsy specimens were required for diagnosis of both agents in 3 patients. HSV esophagitis alone was found in 2 patients; diagnostic viral inclusions were present in the first 3 biopsies in each patient. Thirty-five patients had HIV-associated idiopathic esophageal ulcer; only one of these patients was misdiagnosed. Conclusions: At least 10 biopsies may be required to exclude viral esophagitis in HIV-infected patients. If biopsy specimens are adequate and no evidence of viral cytopathic effect has been found, the patient may be treated on the basis of the results of the initial clinical, endoscopic, and pathologic findings with close clinical follow-up rather than repeat endoscopy. (Gastrointest Endosc 1996;44:587-93.)

Section Review Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Thalidomide in autoimmune conditions

Thalidomide remains a household name 35 years after the disaster caused by its teratogenic properties. Its use re-emerged when the therapeutic benefit of thalidomide in lepromatous leprosy was recognised, and it continues to be used in a small number of patients with a variety of conditions for whom there is no therapeutic alternative. Thalidomide's unique and numerous pharmacological properties have maintained research interest, most recently concentrating on the inhibition of both tumour necrosis factor and angiogenesis. These may be important pharmacological mechanisms in those clinical conditions where it has proven therapeutic benefit. Thalidomide is beneficial in idiopathic oral and genital ulceration, and the similar ulceration of Behcet's disease and human immunodeficiency virus (HIV) infection. In addition, it is of value in chronic graft-versus-host disease, lepromatous leprosy and in a number of rare dermatoses. However, the current use of thalidomide is overshadowed by the tragedy of around 12...

Esophageal Ulcers in AIDS

Letters15 May 1996Esophageal Ulcers in AIDSLouis-Jean Couderc, MD, Evelyne Balloul, MD, and Isabelle Caubarrere, MDLouis-Jean Couderc, MDHopital Foch; 92150 Suresnes, FranceSearch for more papers by this author, Evelyne Balloul, MDHopital Foch; 92150 Suresnes, FranceSearch for more papers by this author, and Isabelle Caubarrere, MDHopital Foch; 92150 Suresnes, FranceSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Wilcox and colleagues [1] documented the high prevalence of idiopathic esophageal ulcers in patients with human immunodeficiency virus (HIV) infection and suggested that steroids be used in these patients. We previously reported that thalidomide was beneficial for esophageal ulceration and the HIV wasting syndrome [2, 3]. With treatment, the symptoms of aphthous ulceration, myalgia, and fever abated within 2 weeks. The patients required prolonged maintenance therapy because of recurrence when the daily thalidomide dose was tapered from 100 mg to 50 mg. No neurologic adverse effects occurred, although patients were treated simultaneously with azidothimidine. We suggest that ...

Esophageal Ulcers in AIDS

Letters15 May 1996Esophageal Ulcers in AIDSPere Domingo, MD, Josep Ris, MD, and Joaquin Lopez-Contreras, MDPere Domingo, MDUniversitat Autonoma de Barcelona; Barcelona, SpainSearch for more papers by this author, Josep Ris, MDUniversitat Autonoma de Barcelona; Barcelona, SpainSearch for more papers by this author, and Joaquin Lopez-Contreras, MDUniversitat Autonoma de Barcelona; Barcelona, SpainSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest the recent report by Wilcox and associates [1] and noted two outstanding findings: 1) the high prevalence of idiopathic esophageal ulcers and the excellent initial response to prednisone therapy and 2) the high percentage of patients with ulcer recurrence. In 13 of 35 patients with esophageal ulcers (37.1%), ulcerations recurred despite an initial clinical and endoscopic response [1].We have recently cared for seven HIV-infected patients who had idiopathic esophageal ulcers. All had advanced disease. Three patients were initially treated with a 2-week regimen of prednisone, 0.5 mg/kg of body weight per day, ...

Esophageal ulceration in human immunodeficiency virus infection. Causes, response to therapy, and long-term outcome.

To determine the causes of esophageal ulceration, the response rate to currently available therapies, and the long-term outcome in patients with human immunodeficiency virus (HIV) infection. Prospective cohort study. An urban county hospital. Consecutive patients with HIV infection and endoscopically detected esophageal ulceration during a 4-year period. Causes of ulcers were determined from clinical, endoscopic, and pathologic findings. Standard medical therapies for the identified causes were instituted, and ulcer healing was endoscopically confirmed when possible. Symptomatic and endoscopic response to therapy and long-term outcome, including survival. 100 patients with esophageal ulcer were identified. Ulcers caused by cytomegalovirus alone were the most common (n = 45); idiopathic ulcers were almost as frequent (n = 40). Herpes simplex virus esophagitis alone was identified as a cause in only 5 patients. Several potential causes of ulcer were found in 5 patients, including Candida esophagitis in 27 patients. Ten patients developed more than one cause of ulceration during long-term follow-up. Eighty-five patients had specific medical therapy for their identified disorders and had an overall response rate of 98%. Median survival from time of diagnosis was 8.9 months (range, 2 days to > 42 months). A difference in median survival was found between patients with cytomegalovirus esophagitis and those with idiopathic esophageal ulcer (7.6 months compared with 13.1 months; P = 0.03). Given 1) the broad spectrum of causes of esophageal ulceration, 2) that each of these causes requires specific therapy, and 3) the apparent high response rate, it is important to do endoscopic evaluation with mucosal biopsy in patients with HIV infection so that a diagnosis can be established and appropriate therapy instituted. Despite effective therapy, long-term survival is poor; however, long-term remission and survival may occur in some patients.

ESOPHAGEAL INFECTIONS

Infections of the esophagus are unusual in the general population and strongly imply immunodeficiency, although immunocompetent individuals are not exempt. HIV infection is predominant among risk factors for infectious esophagitis. For all immunocompromised patients, the most frequently identified esophageal pathogens are Candida, CMV, and HSV. Peculiar to HIV-infected patients are idiopathic esophageal ulcers as well as unusual bacteria and parasites. Patterns of presentation differ with each infecting organism, and clinical features should be used as a guide in achieving a correct diagnosis. For example, a patient with AIDS presenting with esophageal symptoms and thrush, along with abdominal pain, nausea, vomiting, and fever, is unlikely to resolve all symptoms with empiric antifungal therapy alone. Parsimony of diagnosis does not hold among immunodeficient patients in whom concurrent infections are common. Accurate and timely diagnoses are essential as effective treatments are available for particular etiologies. Finally, among immunocompromised patients, all esophageal symptoms are not necessarily due to an infection, and possible diagnoses of pill esophagitis, acid-peptic injury, or structural and functional abnormalities should not be overlooked.

Esophageal Disease in Human Immunodeficiency Virus Infection

Up to 40% of patients with the acquired immunodeficiency syndrome may develop symptoms of esophageal disease. Candida esophagitis is responsible for the majority of the cases of esophageal disease; cytomegalovirus, herpes simplex, idiopathic esophageal ulcers, and Kaposi's sarcoma account for most of the remaining cases. Although endoscopy with esophageal biopsy and brushing is the gold standard for the diagnosis of esophageal disease in the acquired immunodeficiency syndrome, we generally recommend initial empiric therapy with an antifungal agent in patients with esophageal symptoms. Since effective treatment is available for most cases of esophageal disease in the acquired immunodeficiency syndrome, we recommend endoscopic evaluation in patients who do not respond to empiric therapy within 1 to 2 weeks.

Idiopathic esophageal ulceration in the acquired immunodeficiency syndrome: radiologic reappraisal in 10 patients.

Idiopathic esophageal ulceration in patients with AIDS has previously been described. Establishing this diagnosis is important because of the excellent response of these ulcers to corticosteroid therapy. We studied 10 such patients with esophagography and endoscopy. HIV was isolated from the ulcer base in six of the 10 patients utilizing various techniques including in situ hybridization. No other organisms were found. All of the ulcers were in the distal half of the esophagus and were solitary in eight of the 10 patients. The solitary ulcers were large (2.5 x 2.0 cm to 12 x 9 cm) and deep (> 0.5 cm) with undermined margins. In three patients, fistulae arose from the distal esophagus and crossed the gastroesophageal junction. In one patient, a huge idiopathic ulcer perforated into the mediastinum. These latter findings are not seen in the more common ulcerating AIDS esophagitides due to herpes simplex and cytomegalovirus.

Endoscopic Characterization of Idiopathic Esophageal Ulceration Associated with Human Immunodeficiency Virus Infection

Idiopathic esophageal ulcerations (IEUs) associated with human immunodeficiency virus (HIV) infection are now recognized as an important cause of esophageal disease in this population. Limited radiographic and endoscopic reports have almost uniformly described these lesions as solitary and giant. Over a 28-month period, we identified 68 IEUs endoscopically in 23 patients. Most patients had long-standing HIV infection and a low CD4(+) lymphocyte count. Multiple ulcers were identified in 57% of endoscopies. Giant ulcers were seen in one-third, with 37% < or = 1 cm in greatest dimension. Most of the lesions were in the mild- to distal esophagus. The ulcers were characterized as either shallow or intermediate in depth in 53%, with a deep ulcer in 7%. A "heaped-up" appearance of the ulcer was identified in 40%. An esophageal mucosal bridge(s) was seen in two patients. In contrast to previous reports, IEUs are variable endoscopically in number, size, and appearance. Given this lack of uniformity in appearance, which may mimic other causes of esophageal ulceration, all HIV-infected patients with an esophageal ulceration should undergo endoscopy with biopsy to obtain a definitive diagnosis.

Chronic idiopathic esophageal ulceration in the acquired immunodeficiency syndrome. Characterization and treatment with corticosteroids.

Study objectives were to characterize the clinical syndrome of chronic idiopathic esophageal ulceration in patients with acquired immunodeficiency syndrome (AIDS), to determine the extent of local human immunodeficiency virus (HIV) infection, and to evaluate the effect of corticosteroid therapy upon symptoms and healing. Twelve AIDS patients with chronic esophageal ulcers whose etiology remained unknown after clinical evaluation were the subjects. All patients complained of severe odynophagia, chest pain, and weight loss. Barium radiography and endoscopy demonstrated large, undermined ulcers with severe acute inflammation. No evidence of herpes simplex viruses I or II, cytomegalovirus, fungi, or tumors were found histologically. Evidence of HIV was found in all ulcers using a combination of RNA in situ hybridization, immunohistochemistry, and quantitative antigen capture enzyme-linked immunosorbent assay of tissue homogenates. Steroid therapy by the oral or intravenous routes or by direct intralesional injection resulted in pain relief, weight gain in 10 patients, and ulcer healing in five patients. A characteristic clinical syndrome of chronic idiopathic esophageal ulceration may occur in patients with AIDS, related to local HIV infection in the esophagus. Corticosteroids relieve symptoms and may promote healing of the ulcer.

A pilot study of oral corticosteroid therapy for idiopathic esophageal ulcerations associated with human immunodeficiency virus infection

purpose: To evaluate the efficacy and safety of oral prednisone therapy for idiopathic esophageal ulcerations (IEU) associated with human immunodeficiency virus (HIV) infection. patients and methods: Over a 14-month period, all HIV-infected patients with IEU as defined by clinical, endoscopic, and pathologic criteria were prospectively identified. Prednisone was initiated at a dose of 40 mg/d orally, tapering 10 mg/wk, for a total of 1 month of therapy. Patients were closely followed to determine the response to therapy as well as the occurrence of any side effects related to prednisone. All patients were requested to undergo endoscopy within 1 week of the completion of therapy. results: Of 14 patients identified with IEU, 12 consented to prednisone therapy. The mean duration of esophageal symptoms was 2.9 weeks, and odynophagia was the most common presenting symptom. Ten of 12 patients had the acquired immunodeficiency syndrome. Eleven of the 12 patients (92%) had a complete symptomatic response, usually within the first week of therapy. In some patients, the response was dramatic such that oral intake could be rapidly resumed and discharge from the hospital possible. Two patients completed 2 and 3 weeks of therapy, respectively, prior to death, both with a complete symptomatic response. Endoscopic re-examination in seven patients demonstrated complete ulcer healing in all six symptomatic responders, but a persistent ulceration in the one nonresponder. The oral corticosteroid regimen was well tolerated. Mild asymptomatic Candida esophagitis was identified in three of seven patients undergoing follow-up endoscopy. One patient developed self-limited herpes zoster during therapy. No systemic opportunistic infections were documented during or within 1 month of the completion of therapy. conclusions: Oral corticosteroid therapy appears to be a highly efficacious and safe therapy for HIV-associated IEU. Further controlled studies will be necessary to conclusively establish efficacy, as well as determine the optimal dose and duration of therapy.

Roux-limb motility after total gastrectomy and Roux-en-Y anastomosis in patients with Zollinger-Ellison syndrome.

The Roux-en-Y syndrome was defined as chronic nausea, intermittent vomiting, and chronic abdominal pain worsened by eating in patients who have undergone a gastrojejunostomy Roux-en-Y reconstruction for peptic ulcer. When these patients fasted, the Roux limb showed striking abnormalities in motor function; when postprandial, they failed to convert to normal fed-state motor activity. In contrast, patients with Zollinger-Ellison syndrome do well after similar surgery; they can eat most foods and maintain their body weight. We studied the motility of the Roux limb and jejunum in six patients with Zollinger-Ellison after an esophagojejunostomy Roux-en-Y anastomosis. Roux-limb motor activity in these patients, as characterized by the migrating motor complex, was more frequent, well organized, and in synchrony with the remaining jejunum; most subjects also converted to the fed state after a liquid meal. We suggest that the enteric nervous system is intact and functions normally in patients who have had a Roux-en-Y reconstruction for ulcer disease secondary to Zollinger-Ellison, but not in patients with idiopathic peptic ulcer disease.

MISOPROSTOL—A LOGICAL THERAPEUTIC APPROACH TO GASTRODUODENAL MUCOSAL INJURY INDUCED BY NON-STEROIDAL ANTI-INFLAMMATORY DRUGS?

Misoprostol is a synthetic analogue of naturally occurring prostaglandin E1. The basis of the damaging actions of non-steroidal anti-inflammatory drugs (NSAIDs) on the gastrointestinal (GI) tract is believed to be a consequence of two events: a direct damaging action on mucosal integrity and depletion of endogenous mucosal prostaglandins (PGs). Due to the latter effect, and because current evidence indicates that PGs play an important role in maintaining the integrity of the GI tract, misoprostol has been developed as a logical therapy to prevent and heal gastric and duodenal damage caused by NSAIDs. The purpose of this review is to consider the need for such a therapy, to describe its pharmaceutical development, to review its pharmacology and to review its efficacy compared with other available agents.

HIV-1 gp41 Antigen Demonstration in Esophageal Ulcers with Acquired Immunodeficiency Syndrome

Esophageal ulcers associated with acquired immunodeficiency syndrome (AIDS) may be chronic, debilitating, and resistant to antifungal or antiviral therapy. The therapeutic management of these lesions remains controversial due to the difficulty in identifying pathogenic agent(s). We review previously published cases and describe three AIDS patients with esophageal ulcers that stained by immunoperoxidase techniques for human immunodeficiency virus (HIV)-1 surface glyloprotein (gp41). All three showed symptomatic resolution and healing of their ulcers with corticosteroid therapy. We believe this documentation of HIV-1 gp41 antigen within mononuclear cells of esophageal ulcers in AIDS supports a role of the HIV-1 virus in the pathophysiology of idiopathic esophageal ulcers in patients with AIDS. These cases further support a role for corticosteroid therapy in the treatment of esophageal ulcers resistant to antifungal and antiviral therapy in patients with AIDS.

Helicobacter Pylori: Aggressor or Innocent Bystander?

Helicobacter pylori seeks gastric mucosa, whether found in the stomach, duodenum, or Barrett's esophagus. Definitive diagnosis can be secured by appropriate stains of mucosal biopsies and culture, but the rapid urease test, breath isotope studies, and serologic testing are also useful. The frequency of colonization increases with advancing age, but infection occurs earlier in underdeveloped countries. Although the reservoir is uncertain, water or food transmission seems likely. There is sufficient evidence to assign an etiologic role to the bacteria in the causation of type B antral gastritis. H. pylori is found in areas of gastric metaplasia within the duodenum and is associated with duodenitis. Although acute infection leads to hypochlorhydria, chronic colonization has little effect on acid secretion. Studies have thus far failed to establish a convincing relationship between H. pylori and nonulcer dyspepsia, although the bacteria may play a role in selected patients. H. pylori is found in association with most idiopathic gastric and duodenal ulcers, but it is unclear as to whether the bacteria plays a causative or permissive role. The organism has a predilection for intercellular spaces and the mucous layer, thus affording relative isolation from luminally active antibiotics. Monotherapy with bismuth preparations transiently eliminates the bacteria, but recolonization is rapid, probably due to regrowth of sequestered organisms. A combination of metronidazole, bismuth, and tetracycline (or amoxicillin) affords the best eradication rate, but the potential side effects of this program should be considered. The present therapy of duodenal ulcer disease is effective and without significant risk. Treatment of H. pylori should be reserved for those patients who relapse on adequate maintenance therapy. If a safe and effective antibiotic becomes available, more frequent testing and earlier treatment intervention may become more attractive. H. pylori is probably an "innocent bystander" for most patients, but the bacteria may sufficiently impair the defenses of the antral and duodenal mucosa to facilitate the development and relapse of ulcer disease in subsets of patients.

Irradiation-Induced Duodenal Ulcer Disease Refractory to Ranitidine

In two patients duodenal ulcer refractory to high dose H2-blocker treatment started several months after irradiation therapy following right nephrectomy because of renal adenocarcinoma. Established antiulcer drugs like ranitidine, famotidine, sucralfate, pirenzepine, and antacids alone or in combination were unable to control ulcer pain and failed to induce ulcer healing. Initiation of omeprazole treatment at dosages to produce complete achlorhydria were necessary for ulcer healing and maintenance therapy. We suggest that (a) irradiation may cause duodenal ulcer disease indistinguishable from idiopathic duodenal ulcer; (b) radiation-induced ulcers in the duodenal bulb are refractory to various antiulcer drugs but may heal after administration of omeprazole in dosages that completely suppress acid secretion.

Zollinger-Ellison Syndrome in the Intensive Care Setting

Management of patients with Zollinger-Ellison syn drome differs markedly from management of patients with idiopathic gastric acid hypersecretion or routine peptic ulcer disease. Because of the possible complica tions arising from gastric acid hypersecretion or from complications caused by the gastrinoma itself, patients with these disorders frequently present to critical care physicians. It is important that critical care physicians be familiar with the acute presentation of patients with Zollinger-Ellison syndrome as well as the appropriate treatment. We review the important points pertaining to the recognition and treatment of Zollinger-Ellison syn drome in the acute care setting.